A5000993558- Thyroid Disorders and Treatments
- Thyroid Cancer Diagnosis and Treatment
- Hedgehog Signaling Pathway Studies
- Cancer-related Molecular Pathways
- Growth Hormone and Insulin-like Growth Factors
- Cancer and Skin Lesions
- Muscle Physiology and Disorders
- Digestive system and related health
- Cancer Cells and Metastasis
- Cancer, Hypoxia, and Metabolism
- FOXO transcription factor regulation
- Cytokine Signaling Pathways and Interactions
- Pituitary Gland Disorders and Treatments
- Genetics and Neurodevelopmental Disorders
- Oral and Maxillofacial Pathology
- Wnt/β-catenin signaling in development and cancer
- Epigenetics and DNA Methylation
- Electrospun Nanofibers in Biomedical Applications
- Hair Growth and Disorders
- Antiplatelet Therapy and Cardiovascular Diseases
- Cancer-related gene regulation
- NF-κB Signaling Pathways
- Ion channel regulation and function
- Congenital heart defects research
- Platelet Disorders and Treatments
University of Naples Federico II
2004-2025
SDN Istituto di Ricerca Diagnostica e Nucleare
2010-2023
Istituti di Ricovero e Cura a Carattere Scientifico
2010-2023
Federico II University Hospital
2023
Institute of Genetics and Biophysics
2002-2004
Universidad de Alcalá
1993
The Sonic hedgehog (Shh) pathway plays a critical role in hair follicle physiology and is constitutively active basal cell carcinomas (BCCs), the most common human malignancy. Type 3 iodothyronine deiodinase (D3), thyroid hormone-inactivating enzyme, frequently expressed proliferating neoplastic cells, but its this context unknown. Here we show that Shh, through Gli2, directly induces D3 keratinocytes mouse BCCs. We demonstrate Gli-induced reduces intracellular hormone, thus resulting...
The active thyroid hormone 3,5,3′ triiodothyronine (T3) is a major regulator of skeletal muscle function. deiodinase family enzymes controls the tissue-specific activation and inactivation prohormone thyroxine (T4). Here we show that type 2 (D2) essential for normal mouse myogenesis regeneration. Indeed, D2-mediated increases in T3 were enhanced transcription myogenic differentiation 1 (MyoD) execution program. Conversely, expression T3-dependent genes was reduced after injury regeneration...
Abstract Context: A substantial proportion of athyreotic levothyroxine (LT4)-treated patients experience hypothyroid-like symptoms. During LT4 replacement, levels the active hormone triiodothyronine (T3) strictly depend on type 2-deiodinase (D2)-mediated activation LT4. The Thr92Ala polymorphism and 258 G/A in DIO2 gene have been associated with various clinical conditions. Objectives: To investigate effects polymorphisms thyroid homeostasis. Design: We compared presurgical hormonal status...
Precise control of the thyroid hormone (T3)-dependent transcriptional program is required by multiple cell systems, including muscle stem cells. Deciphering how this achieved and T3 signal controlled in niches essentially unknown. We report that response to proliferative stimuli such as acute skeletal injury, type 3 deiodinase (D3), hormone-inactivating enzyme, induced satellite cells where it reduces intracellular signaling. Satellite cell-specific genetic ablation dio3 severely impairs...
Abstract Ankyloblepharon‐ectodermal defects‐cleft lip/palate (AEC) syndrome, which is characterized by cleft palate and severe defects of the skin, an autosomal dominant disorder caused mutations in gene encoding transcription factor p63. Here, we report generation a knock‐in mouse model for AEC syndrome ( p63 +/L514F ) that recapitulates human disorder. The mutation exerts selective dominant‐negative function on wild‐type affecting progenitor cell expansion during ectodermal development...
Ankyloblepharon, ectodermal defects, cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder caused by mutations in the p63 gene, essential for embryonic development of stratified epithelia. The most severe cutaneous manifestation this long-lasting skin fragility associated with erosions after birth. Using knock-in mouse model AEC syndrome, we found that was microscopic blistering between basal and suprabasal compartments epidermis reduced desmosomal contacts. Expression...
Abstract Thyroid hormone is a pleiotropic factor that controls many cellular processes in multiple cell types such as cancer stem cells (CSC). concentrations the blood are stable, but action of deiodinases (D2–D3) provides cell-specific regulation thyroid activity. Deregulation deiodinase function and status has been implicated tumorigenesis. Therefore, we investigated role metabolism signaling colorectal CSCs (CR-CSC), where control division chemosensitivity. We found increased...
Abstract Epithelial tumor progression often involves epithelial-mesenchymal transition (EMT). We report that increased intracellular levels of thyroid hormone (TH) promote the EMT and malignant evolution squamous cell carcinoma (SCC) cells. TH induces by transcriptionally up-regulating ZEB-1, mesenchymal genes metalloproteases suppresses E-cadherin expression. Accordingly, in human SCC, elevated D2 (the T3-producing enzyme) correlates with grade is associated an risk postsurgical relapse...
Thyroid hormone (TH) is a key metabolic regulator that acts by coordinating short- and long-term energy needs. Accordingly, significant changes are observed depending on thyroid status. Although it established hyperthyroidism augments basal consumption, thus resulting in an enhanced state, the net effects cellular respiration generation of reactive oxygen species (ROS) remain unclear. To elucidate augmented TH signal muscle cells, we generated doxycycline-inducible cell line which expression...
Abstract Fibro-adipogenic progenitor cells (FAPs) are a heterogeneous population of multipotent mesenchymal that give rise to fibroblasts and adipocytes. In response muscle injury, FAPs activated cooperate with inflammatory stem promote regeneration. pathological conditions, such as muscular dystrophies, this coordinated is partially lost an accumulation observed which responsible for maladaptive fibrosis, ectopic fat deposition impaired The role intracellular thyroid hormone (TH) signaling...
The thyroid hormone–inactivating (TH-inactivating) enzyme type 3 iodothyronine deiodinase (D3) is an oncofetal protein that rarely expressed in adult life but has been shown to be reactivated the context of proliferation and neoplasms. D3 terminates TH action within tumor microenvironment, thereby enhancing cancer cell proliferation. However, pathological role contribution metabolism have yet fully explored. Here, we describe a reciprocal regulation between cancer-associated microRNA-21...
The p63 gene encodes a master regulator of epidermal commitment, development, and differentiation. Heterozygous mutations in the C-terminal domain can cause ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, life-threatening disorder characterized by skin fragility severe, long-lasting erosions. Despite deep knowledge functions, little is known about mechanisms underlying disease pathology possible treatments. Here, we show that multiple AEC-associated mutations, but not...
The type 2 iodothyronine deiodinase (D2) is essential for feedback regulation of TSH by T4. We genetically inactivated in vivo D2 thyrotrophs using a mouse model Cga-driven cre recombinase. Pituitary activity was reduced 90% the Cga-cre knockout (KO) mice compared with control Dio2(fl/fl) mice. There no growth or reproductive phenotype. Basal levels were increased 1.5- to 1.8-fold, but serum T4 and T3 not different from controls adult In hypothyroid mice, suppression T4, T3, impaired....
The sodium/iodide symporter (NIS) is a plasma membrane protein that mediates active iodide transport in thyroid and mammary cells. It prerequisite for radioiodide treatment of cancer promising diagnostic therapeutic tool breast cancer. We investigated the molecular mechanisms governing NIS expression Here we report Nkx-2.5, cardiac homeobox transcription factor also expressed primordium, potent inducer promoter. By binding to two specific promoter sites (N2 W), Nkx-2.5 induced rNIS (about...
The proliferation and differentiation of muscle precursor cells require myogenic regulatory factors chromatin modifiers whose concerted action dynamically regulates access to DNA allows reprogramming towards terminal differentiation. Type 2 deiodinase (D2), the thyroid hormone (TH)-activating enzyme, is sharply upregulated during myoblast differentiation, whereas type 3 (D3), TH-inactivating downregulated. molecular determinants controlling synchronized D2 D3 expression in are completely...
Thyroid hormone (TH) is an important regulator of growth, development, and metabolism. Most the active TH T3 generated by peripheral metabolism mediated iodothyronine deiodinases. Type 3 deiodinase (D3) inactivates via specific deiodination reactions. It oncofetal protein frequently expressed in neoplastic tissues a direct target sonic hedgehog (Shh) pathway basal cell carcinomas (BCCs). However, molecular mechanisms triggered BCC are still mostly unrevealed. Here, we demonstrate that D3...
Thyroid hormones (THs) mediate pleiotropic cellular processes involved in metabolism, proliferation, and differentiation. The intracellular hormonal environment can be tailored by the type 1 2 deiodinase enzymes D2 D3, which catalyze TH activation inactivation respectively. In many systems, THs exert well-documented stimulatory or inhibitory effects on cell proliferation; however, molecular mechanisms they control rates of cycle progression have not yet been entirely clarified. We previously...
p63 is a crucial regulator of epidermal development, but its transcriptional control has remained elusive. Here, we report the identification long-range enhancer (p63LRE) that composed two evolutionary conserved modules (C38 and C40), acting in concert to tissue- layer-specific expression gene. Both are an open active chromatin state human mouse keratinocytes embryonic epidermis, strongly bound by p63. p63LRE activity dependent on skin, also commitment induced pluripotent stem cells toward...
Thyroid transcription factor gene 1 (TTF-1) is a homeobox-containing involved in thyroid organogenesis.During early development, the homeobox Nkx-2.5 expressed precursor cells coincident with appearance of TTF-1.The aim this study was to investigate molecular mechanisms underlying thyroid-specific expression.We show that C terminus interacts TTF-1 homeodomain and, moreover, expression dominant-negative isoform (N188K) reduces TTF-1-driven by titrating away from its target DNA.This process...